In building the National Cancer Institute (NCI) Cancer Research Data Commons (CRDC), the NCI aims to support cancer research initiatives through sustaining multidisciplinary bioinformatics resources. A multidisciplinary approach is paramount to our improved understanding of the molecular underpinnings of cancer. The CRDC will include multiple digital data knowledge bases, or Nodes, and other informatics resources each centered on different research and clinical data types such as genomics, proteomics, and imaging. NCI is managing an ongoing effort to create a re-usable Framework for the development of Commons Nodes. The Framework includes guidelines related to: security, data submission and validation, data models, discoverability of data and tools, application programming interfaces (APIs), container environments, and user workspaces. Through fostering community-driven, open development informatics initiatives, the CRDC will create, maintain, and extend informatics infrastructure and standards to improve interoperability among disparate information systems and data types. As a Node in the CRDC, the overarching goal of the NCI Proteomic Data Commons (PDC) pilot project is to democratize access to cancer-related proteomic datasets as well as to provide sustainable computational support to the cancer research community. To foster collaboration and accelerate discovery, NCI aims to enhance data sharing within the cancer proteomics community and beyond. The PDC seeks to enable and empower the cancer-research community, including scientists working in both intramural and extramural laboratories, with the necessary informatics capabilities to carry out large-scale, multi-omic data analysis. Researchers? ability to access diverse datasets, and perform robust and reproducible analyses is currently stifled by the siloed nature of the current informatics infrastructure. As a Node of the NCI CRDC, the PDC will overcome current data access limitations by co-localizing proteomics data and analysis tools within a larger data ecosystem that supports multiple research and clinical data types.